Nitrofurantoin, chemically known as 1-[(5-nitrofurfurylidene)amino]hydantoin, is a well-known antibacterial agent for the treatment of urinary tract infections. The drug is remarkably well tolerated in humans, the most frequent adverse reactions involving complaints of anorexia, nausea and emesis.
Numerous attempts have been made to alleviate these undesirable side effects and at the same time provide a dosage form requiring less frequent administration that is essentially biologically equivalent to the standard 100 mg tablet of nitrofurantoin administered four times daily.
Attempts to minimize these side-effects such as diet control, the combination of nitrofurantoin with other substances, enteric coated tablets and reduced dosage regimens have not proven successful. U.S. Pat. No. 3,401,221 discloses crystals of nitrofurantoin, substantially cubic in form that are capable of passing through a 50 U.S. mesh screen but not through a 400 U.S. mesh screen. Administration of the drug in the form of such large crystals is stated to reduce in some degree the nausea and emesis side-effects obtained. There still remain, however, a relatively minor, but nevertheless substantial, number of patients who are deprived of the benefits of this useful drug because of these undesirable side-effects.
Additionally, in order to improve upon the efficacy of nitrofurantoin in the treatment of urinary infections, efforts must be directed to provide more of a prompt physiologic disposition of the drug at the situs of infection, i.e., a more rapid urinary excretion of the unaltered drug in effective concentrations and amounts upon oral administration. The administration of nitrofurantoin having a relatively large crystal size so as to reduce the incidence of nausea and emesis, concomitantly results in delayed urinary excretion and reduced urinary concentrations of the unaltered drug.